Is it all in the family? Sexual identity differences in DSM-5 alcohol and other drug use disorders and associations with alcohol and other drug misuse history among parents, offspring, and other relatives.

Background: The objectives of this study were to: (1) estimate the prevalence of family history of alcohol and other drug (AOD) misuse (positive family history [FH+]) in first- and second-degree relatives across sexual identity subgroups (i.e., lesbian, gay, bisexual, heterosexual); (2) compare AOD misuse among offspring of sexual minority and heterosexual parents; and (3) examine the relationships between FH+ and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) alcohol use disorder (AUD) and other drug use disorder (ODUD) across sexual identity subgroups. Methods: Data were from the National Epidemiologic Survey on Alcohol and Related Conditions-III (n = 36,309 non-institutionalized U.S. adults aged ≥ 18 years). Data collection occurred in households using structured diagnostic face-to-face interviews during 2012-2013. Results: The presence of FH+ in first- and second-degree relatives was most prevalent among bisexual women relative to all other sexual orientation subgroups. Multivariable regression analyses indicated that the odds of AUD and ODUD were higher among FH+ adults relative to negative family history (FH-) adults. Lesbian and bisexual women had higher odds of AUD compared to heterosexual women, controlling for any FH+; this sexual identity difference was not found for men. There were no significant differences in ODUD between heterosexual FH- men and gay FH- men. We found differences in AOD misuse among offspring of bisexual parents, but not gay or lesbian parents compared to heterosexual parents. Conclusions: Health professionals should consider the higher likelihood of a family history of AOD misuse among sexual minorities, especially bisexual women, when treating these individuals. The lack of differences in AOD misuse among offspring of gay or lesbian parents relative to heterosexual parents warrants attention for legal, policy, and clinical decisions.

Pre-school Skills and School-Age Reading Comprehension in Children on the Autism Spectrum: A Preliminary Investigation.

We explored reading comprehension development in children on the spectrum from pre-school to the first (YOS1) and third year of schooling (YOS3). Children were first assessed on meaning-related skills in pre-school. Forty-one children completed follow-up assessments of reading comprehension, reading accuracy, and listening comprehension in YOS1. Nineteen returned for assessments of reading accuracy, reading comprehension, and listening comprehension in YOS3. Children showed poorer reading comprehension than reading accuracy at both timepoints. Reading comprehension, reading accuracy, and listening comprehension were significantly concurrently correlated. Pre-school receptive vocabulary was a significant predictor of YOS3 reading comprehension. Results from this preliminary investigation highlight the potential for early identification of children on the spectrum at risk for reading comprehension difficulties.

Sexual orientation differences in childhood sexual abuse, suicide attempts, and DSM-5 alcohol, tobacco, other drug use, and mental health disorders in the US.

BACKGROUND: Childhood sexual abuse (CSA) contributes to increased risk of substance use and mental health disorders in the general population. OBJECTIVE: To assess the prevalence and associations of CSA and suicide attempts, substance use, and mental health disorders as a function of sex (female, male) and sexual orientation (lesbian, gay, bisexual, heterosexual-identified with same-sex attraction and/or behavior, heterosexual-identified without same-sex attraction and/or behavior, and unsure). PARTICIPANTS AND SETTING: Data were collected using structured diagnostic face-to-face interviews in a nationally representative sample of 36,309 US adults. METHODS: We used descriptive statistics and logistic regression modeling to analyze data from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III). RESULTS: Childhood sexual abuse was most prevalent among sexual minorities, especially bisexual females. Nearly one-third of bisexual females (30.6%) reported experiencing two or more types of CSA, p < .001. Among all participants, exposure to one or more types of CSA was associated with greater odds of lifetime suicide attempts, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) alcohol, tobacco or other drug use disorder, and mental health disorders, after adjusting for other childhood adversity/maltreatment and general life stressors. CONCLUSIONS: Sexual minority females and males in the US are more likely than their heterosexual counterparts to report CSA. Higher risk of suicide attempts and DSM-5 alcohol, tobacco, other drug use, and mental health disorders in adulthood was directly associated with CSA, particularly among bisexual females. Health professionals working with individuals who have experienced CSA should assess these risks and intervene as needed.

Body composition predicts mortality and decompensation in compensated cirrhosis patients: A prospective cohort study.

BACKGROUND & AIMS: Body composition, particularly sarcopenia, is associated with mortality in patients with decompensated cirrhosis undergoing transplant evaluation. Similar data are limited for non-transplant eligible or compensated patients. METHODS: A total of 274 patients with cirrhosis were followed prospectively for ≤5 years after a CT scan. We utilized Analytic Morphomics® to measure body composition (fat, muscle, and bone) which was rendered into relative values (percentiles) in relation to a reference population. The model for end-stage liver disease (MELD) score was used as a reference model for survival prediction. We validated our models in a separate cohort. RESULTS: Our cohort had a mean Child-Pugh score of 7.0 and a mean MELD of 11.3. The median follow-up time was 5.05 years. The proportion of patients alive at 1, 3 and 5 years was 86.5%, 68.0%, and 54.3%; 13 (4.6%) underwent liver transplantation. Child-Pugh B/C (vs. A) cirrhosis was associated with decreased muscle, subcutaneous, and visceral fat area but increased subcutaneous/visceral fat density. Decreased normal density muscle mass was associated with mortality (hazard ratio [HR] 0.984, p <0.001) as well as visceral and subcutaneous fat density (HR 1.013 and 1.014, respectively, p <0.001). Models utilizing these features outperformed MELD alone for mortality discrimination in both the derivation and validation cohort, particularly for those with compensated cirrhosis (C-statistics of 0.74 vs. 0.58). Using competing risk analysis, we found that subcutaneous fat density was most predictive of decompensation (subdistribution HR 1.018, p = 0.0001). CONCLUSION: The addition of body composition features to predictive models improves the prospective determination of prognosis in patients with cirrhosis, particularly those with compensated disease. Fat density, a novel feature, is associated with the risk of decompensation. LAY SUMMARY: Am I at high risk of getting sicker and dying? This is the key question on the mind of patients with cirrhosis. The problem is that we have very few tools to help guide our patients, particularly if they have early cirrhosis (without symptoms like confusion or fluid in the belly). We found that how much muscle and fat the patient has and what that muscle or fat looks like on a CT scan provide helpful information. This is important because many patients have CT scans and this information is hiding in plain sight.

Skin complications associated with vascular access devices: A secondary analysis of 13 studies involving 10,859 devices.

BACKGROUND: Vascular access devices are widely used in healthcare settings worldwide. The insertion of a vascular access device creates a wound, vulnerable to irritation, injury and infection. Vascular access-associated skin complications are frequently reported in the literature, however very little evidence is available regarding the incidence and risk factors of these conditions to inform practice and technology development. OBJECTIVES: To estimate the incidence of vascular access-associated skin complications, and to identify patient, catheter and healthcare-related characteristics associated with skin complication development. DESIGN: Secondary data analysis from 13 multi-centre randomised controlled trials and observational studies evaluating technologies and performance of vascular access devices in clinical settings between 2008 and 2017. SETTINGS: Six hospitals (metropolitan and regional) in Queensland, Australia. PARTICIPANTS: The 13 studies involved paediatric and adult participants, across oncology, emergency, intensive care, and general hospital settings. A total of 7669 participants with 10,859 devices were included, involving peripheral venous (n = 9933), peripheral arterial (n = 341), and central venous access (n = 585) devices. ANALYSIS: Standardised study data were extracted into a single database. Clinical and demographic data were descriptively reported. Cox proportional hazards regression models (stratified by peripheral vs central) were used for time-to-event, per-device analyses to examine risk factors. Univariate associations were undertaken due to complexities with missing data in both outcomes and covariates, with p < 0.01 to reduce the effect of multiple comparisons. RESULTS: Over 12% of devices were associated with skin complication, at 46.2 per 1000 catheter days for peripheral venous and arterial devices (95% confidence interval, CI 42.1-50.7), and 22.5 per 1000 catheter days for central devices (95% CI 16.5-306). The most common skin complications were bruising (peripheral n = 134, 3.7%; central n = 33, 6.8%), and swelling due to infiltration for peripheral devices (n = 296; 2.9%), and dermatitis for central devices (n = 13; 2.2%). The significant risk factors for these complications were predominantly related to device (e.g., skin tears associated with peripheral arterial catheters [hazard ratio, HR 16.0], radial insertion [HR 18.0] basilic insertion [HR 26.0])) and patient characteristics (e.g., poor skin integrity associated with increased risk of peripheral device bruising [HR 4.12], infiltration [HR 1.98], and skin tear [HR 48.4]), rather than management approaches. CONCLUSIONS: Significant skin complications can develop during the life of peripheral and central vascular access devices, and these are associated with several modifiable and non-modifiable risk factors. Further research is needed to evaluate effectiveness technologies to prevent and treat skin complications associated with vascular access devices.

Two-stage genome-wide methylation profiling in childhood-onset Crohn's Disease implicates epigenetic alterations at the VMP1/MIR21 and HLA loci.

BACKGROUND: As a result of technological and analytical advances, genome-wide characterization of key epigenetic alterations is now feasible in complex diseases. We hypothesized that this may provide important insights into gene-environmental interactions in Crohn's disease (CD) and is especially pertinent to early onset disease. METHODS: The Illumina 450K platform was applied to assess epigenome-wide methylation profiles in circulating leukocyte DNA in discovery and replication pediatric CD cohorts and controls. Data were corrected for differential leukocyte proportions. Targeted replication was performed in adults using pyrosequencing. Methylation changes were correlated with gene expression in blood and intestinal mucosa. RESULTS: We identified 65 individual CpG sites with methylation alterations achieving epigenome-wide significance after Bonferroni correction (P < 1.1 × 10(-7)), and 19 differently methylated regions displaying unidirectional methylation change. There was a highly significant enrichment of methylation changes around GWAS single nucleotide polymorphisms (P = 3.7 × 10(-7)), notably the HLA region and MIR21. Two-locus discriminant analysis in the discovery cohort predicted disease in the pediatric replication cohort with high accuracy (area under the curve, 0.98). The findings strongly implicate the transcriptional start site of MIR21 as a region of extended epigenetic alteration, containing the most significant individual probes (P = 1.97 × 10(-15)) within a GWAS risk locus. In extension studies, we confirmed hypomethylation of MIR21 in adults (P = 6.6 × 10(-5), n = 172) and show increased mRNA expression in leukocytes (P < 0.005, n = 66) and in the inflamed intestine (P = 1.4 × 10(-6), n = 99). CONCLUSIONS: We demonstrate highly significant and replicable differences in DNA methylation in CD, defining the disease-associated epigenome. The data strongly implicate known GWAS loci, with compelling evidence implicating MIR21 and the HLA region.